This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Like the skeleton in humans, the cytoskeleton provides the mechanic support for the individual cells. The cytoskeleton is also essential for compartmentation and signal transduction pathways within the cells. There are three types of cytoskeleton: microtubules, microfilaments, and intermediate filaments. These cytoskeletal systems are essentially composed by simple subunits that in turn form polymers to give rise to the final filamentous form. Unlike microtubules and microfilaments, which are formed by cytosolic tubulin and actin, respectively, intermediate filaments (IFs) are formed by a large family of differentially-expressed genes. Typically, IF can take up to 1~5% of total proteins inside the cells. The disorganization and/or aggregation of IF are a hallmark of many human diseases. The outstanding question is how individual IF subunit assemble into filaments and how the filaments disassemble into subunits in vivo. The goal of this project is to identify the factors required for the assembly and disassembly processes and to delineate the in vivo pathways. Finally, we would like to know whether these pathways are altered in the disease settings and whether the molecules identified in this project can be used as therapeutic targets.